A barrier like no other: What is the blood-brain barrier?

“The blood-brain barrier (BBB) is a unique, tightly packed, layer of cells that line the brain and spinal cord”. 1

The brain is extremely precious and need to be protected – and this is where the BBB comes in: it helps protect the brain from harmful toxins and infection-causing pathogens.2 However, the BBB is also a selective filter which allows essential nutrients/molecules to pass through to the brain.3,4

On this page

  • A barrier like no other: What is the blood-brain barrier?
  • How the blood barrier works: multi-layered protection
  • Why is the BBB important for allergy sufferers and their treatment?
  • Second-generation antihistamines like Allevia® have been developed to address the issues associated with first-generation antihistamines

How the blood barrier works: multi-layered protection

The BBB is an exquisite structure built for purpose. Tight junctions (between cells) are an important feature of the BBB and central to its barrier function.4 -7 The endothelial cells lining the blood vessels throughout the body usually have gaps – or paracellular spaces – between them that allow substance transport and regulation.5-7 However, unlike the rest of the body, the endothelial cells in the BBB have tight junctions between them, that close these gaps creating a physical barrier between the brain and the rest of the body.6,7 Also important to BBB function are glial cells called astrocytes, which help maintain the tight junctions in endothelial cells as well as help regulate the BBB function.8.9 Other specialised cells in the BBB such as pericytes also help to regulate it.10

The BBB is made up of endothelial cells, astrocytes and pericytes11-13 

Why is the BBB important for allergy sufferers and their treatment?

Penetration of the BBB: First- and second-generation antihistamines have different safety characteristics which are largely based on whether they cross the BBB14

­­First-generation antihistamines were developed back in the 1940s and have faithfully been providing symptom relief to millions of people ever since.15 They are characterised by their ability to block the action of histamine, which is heavily involved in the body’s allergic response.16 However, aside from blocking histaminic receptors, first-generation antihistamines also block muscarinic receptors.17,18 This results in side effects such as dry mouth, urinary and gastrointestinal problems.18,19 Importantly, first-generation antihistamines also penetrate the BBB and can therefore, cause central nervous system (CNS) side effects such as drowsiness and sedation.18,20 It is for these reasons, that first-generation antihistamines, while effective, have a weaker safety profile than their second-generation counterparts.11,17,19

“First-generation H1 antihistamines cross the blood-brain barrier, and in usual doses, they potentially cause sedation and impair cognitive function and psychomotor performance”19 

Second-generation antihistamines like Allevia® have been developed to address the issues associated with first-generation antihistamines

While histamine acts via the H1, H2, H3 and H4 receptors, it is the H1 receptor that is most involved in histamine-dependent allergic diseases – and it is precisely the H1 receptor that second-generation antihistamines target.18 In contrast, first-generation antihistamines, also target the H1 receptor but are a little less selective for this key receptor.18

“Therefore, the discovery of compounds selectively acting on H1 receptors, currently called second generation drugs, could be considered the greatest breakthrough during more than 70 years of the history of antihistamines”18

What’s more, unlike first-generation antihistamines, second-generation histamines do not (or very minimally) cross the BBB in most people and so, do not cause serious CNS adverse events (including drowsiness).14,18,20 That said, a minority of consumers can still experience drowsiness with second generation antihistamines.20

Second-generation antihistamines are highly selective for the H1 receptor and so do not (or very minimally) cross the BBB (unlike first-generation antihistamines). They have an improved safety profile (including non-drowsiness in most patients) when compared to first-generation antihistamines.14-20

MAT-XU-2301599 V1.0 (May 2023)


  1. Multiple sclerosis trust. Blood-Brain barrier. Available at:  https://mstrust.org.uk/a-z/blood-brain-barrier Accessed: March 2023.
  2. The University of Queensland. What is the blood-brain barrier: Available at: https://qbi.uq.edu.au/brain/brain-anatomy/what-blood-brain-barrier Accessed: March 2023.
  3. Knox, E.G., Aburto, M.R., Clarke, G. et al. The blood-brain barrier in aging and neurodegeneration. Mol Psychiatry. 2022;27,2659-2673.
  4. Lochhead JJ, Yang J, Ronaldson PT, Davis TP. Structure, Function, and Regulation of the Blood-Brain Barrier Tight Junction in Central Nervous System Disorders. Front Physiol. 2020;11:914.
  5. Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Blood Vessels and Endothelial Cells. Available at: https://www.ncbi.nlm.nih.gov/books/NBK26848/ Accessed: March 2023.
  6. Bauer HC, Krizbai IA, Bauer H, Traweger A. "You Shall Not Pass"-tight junctions of the blood brain barrier. Front Neurosci. 2014;8:392.
  7. Mentor S, Fisher D. High-Resolution Insights Into the in vitro Developing Blood-Brain Barrier: Novel Morphological Features of Endothelial Nanotube Function. Front Neuroanat. 2021;15:661065.
  8. Sofroniew MV, Vinters HV. Astrocytes: biology and pathology. Acta Neuropathol. 2010;119(1):7-35.
  9. Kubotera, H., Ikeshima-Kataoka, H., Hatashita, Y. et al. Astrocytic endfeet re-cover blood vessels after removal by laser ablation. Sci Rep 9. 2019; 1263.
  10. Attwell D, Mishra A, Hall CN, et al. What is a pericyte? J Cereb Blood Flow Metab. 2016;36(2):451-5.
  11. Urs H. Langen, Swathi Ayloo, Chenghua Gu. Development and Cell Biology of the Blood-Brain Barrier. Annu Rev Cell Dev Biol. 2019 Oct 6; 35: 591-613.
  12. American Society for Microbiology. How Pathogens Penetrate the Blood-Brain Barrier. Available at: https://asm.org/Articles/2020/April/How-Pathogens-Penetrate-the-Blood-Brain-Barrier  Accessed: March 2023.
  13. Bayir E, Sendemir A. Role of Intermediate Filaments in Blood-Brain Barrier in Health and Disease. Cells. 2021;10(6):1400
  14. Farzam K, Sabir S, O'Rourke MC. Antihistamines. [Updated 2022 Jul 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022. Available at: https://www.ncbi.nlm.nih.gov/books/NBK538188/ Accessed:  March 2023.
  15. Casale TB, Blaiss MS, Gelfand E, et al. First do no harm: managing antihistamine impairment in patients with allergic rhinitis. J Allergy Clin Immunol. 2003;111(5):S835-42.
  16. White MV. The role of histamine in allergic diseases. J Allergy Clin Immunol. 1990;86(4 Pt 2):599-605.
  17. Liu H, Farley JM. Effects of first and second generation antihistamines on muscarinic induced mucus gland cell ion transport. BMC Pharmacol. 2005;24;5:8.
  18. Kuna P, Jurkiewicz D, Czarnecka-Operacz MM, et al. The role and choice criteria of antihistamines in allergy management - expert opinion. Postepy Dermatol Alergol. 2016;33(6):397-410.
  19. Simons FE, Simons KJ. H1 antihistamines: current status and future directions. World Allergy Organ J. 2008 ;1(9):145-55.
  20. Church MK, Church DS. Pharmacology of antihistamines. Indian J Dermatol. 2013;58(3):219-24.

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That’s why Allevia® helps deliver relief that lasts 24 hours, acts within one hour and is prescription strength, so you can get on with enjoying your day.​